44 research outputs found
IGFBPs mediate IGF-1's functions in retinal lamination and photoreceptor development during pluripotent stem cell differentiation to retinal organoids
Abstract
Development of the retina is regulated by growth factors, such as insulin-like growth factors 1 and 2 (IGF-1/2), which coordinate proliferation, differentiation, and maturation of the neuroepithelial precursors cells. In the circulation, IGF-1/2 are transported by the insulin growth factor binding proteins (IGFBPs) family members. IGFBPs can impact positively and negatively on IGF-1, by making it available or sequestering IGF-1 to or from its receptor. In this study, we investigated the expression of IGFBPs and their role in the generation of human retinal organoids from human pluripotent stem cells, showing a dynamic expression pattern suggestive of different IGFBPs being used in a stage-specific manner to mediate IGF-1 functions. Our data show that IGF-1 addition to culture media facilitated the generation of retinal organoids displaying the typical laminated structure and photoreceptor maturation. The organoids cultured in the absence of IGF-1, lacked the typical laminated structure at the early stages of differentiation and contained significantly less photoreceptors and more retinal ganglion cells at the later stages of differentiation, confirming the positive effects of IGF-1 on retinal lamination and photoreceptor development. The organoids cultured with the IGFBP inhibitor (NBI-31772) and IGF-1 showed lack of retinal lamination at the early stages of differentiation, an increased propensity to generate horizontal cells at mid-stages of differentiation and reduced photoreceptor development at the later stages of differentiation. Together these data suggest that IGFBPs enable IGF-1's role in retinal lamination and photoreceptor development in a stage-specific manner
Birth prevalence of non-syndromic orofacial clefts in Saudi Arabia and the effects of parental consanguinity
Objectives: To describe the characteristics and prevalence of non-syndromic orofacial clefting (NSOFC) and assess the effects of parental consanguinity on NSOFC phenotypes in the 3 main cities of Saudi Arabia.
Methods: All infants (114,035) born at 3 referral centers in Riyadh, and 6 hospitals in Jeddah and Madinah between January 2010 and December 2011 were screened. The NSOFC cases (n=133) were identified and
data was collected through clinical examination and records, and information on consanguinity through parent interviews. The diagnosis was confirmed by reviewing medical records and contacting the infants’ pediatricians. Control infants (n=233) matched for gender and born in the same hospitals during the same period, were selected.
Results: The prevalence of NSOFC was 1.07/1000 births in Riyadh, and 1.17/1000 births overall; cleft lip (CL) was 0.47/1000 births, cleft lip and palate (CLP) was 0.42/1000 births, and cleft palate (CP) was 0.28/1000 births. Cleft palate was significantly associated with consanguinity (p=0.047, odds ratio: 2.5, 95% confidence interval: 1 to 6.46), particularly for first cousin marriages.
Conclusion: The birth prevalence of NSOFC in Riyadh alone, and in the 3 main cities of Saudi Arabia were marginally lower than the mean global prevalence. While birth prevalence for CLP was comparable to global figures, the CL:CLP ratio was high, and only CP was significantly associated with consanguinity
Molecular Screening of <i>VAX1</i> Gene Polymorphisms Uncovered the Genetic Heterogeneity of Non-Syndromic Orofacial Cleft in Saudi Arabian Patients
Objective: Nonsyndromic orofacial cleft (NSOFC) including cleft lip with or without cleft palate (CL±P) and cleft palate (CP) are multifactorial developmental disorders with both genetic and environmental etiological factors. In this study we investigated the association between CL±P and CP, and two polymorphisms previously determined using genome-wide association studies, as well as the association between consanguinity and CL±P and CP.
Methods: DNA was extracted from saliva specimens from 171 triads consisting of affected individuals and their parents, as well as 189 control triads (matched for age, gender, and location) that were recruited from 11 referral hospitals in Saudi Arabia. Two polymorphisms, rs4752028 and rs7078160, located in the VAX1 gene were genotyped using real-time polymerase chain reaction. A transmission disequilibrium test was carried out using the Family-Based Association Test and PLINK (genetic tool-set) to measure the parent-of-origin effect.
Results: Significant differences were found between affected individuals and the control group. In the case of the rs4752028 risk allele in cleft, the phenotypes were: CL±P (fathers: odds ratio [OR] 2.16 [95% CI 1.38–3.4]; mothers: OR 2.39 [95% CI 1.53–3.71]; and infants: OR 2.77 [95% CI 1.77–4.34]) and CP (fathers: OR 2.24 [95% CI 1.15–4.36] and infants: OR 2.43 [95% CI 1.25–4.7]). For CL±P and the rs7078160 risk allele, the phenotypes were: (fathers: OR 1.7 [95% CI 1.05–2.86]; mothers: OR 2.43 [95% CI 1.49–3.97]; and infants: OR 2.34 [95% CI 1.44–3.81]). In terms of consanguinity, we found significant association between consanguinity and the rs4752028 polymorphism minor allele among CL±P compared with controls (p = 0.001).
Conclusion: This is the first study to find a relationship between these two loci on 10q25 (rs4752028 and rs7078160) and NSOFC in a population with high levels of consanguinity
Attitudes towards mandatory national premarital screening for hereditary hemolytic disorders
Background A compulsory national premarital screening (PMS) program for hereditary hemoglobinopathies was established in the Kingdom of Saudi Arabia (KSA) in February 2004. Termination of pregnancy of affected fetuses is not widely acceptable. Many couples decide to get married regardless of the result. A trend towards coercive interference with this decision is emerging.Objectives To examine the attitude of young educated individuals regarding the national PMS program and its implementation.Methods Eight hundred university students (aged 18-29) filled in a self-administered structured questionnaire. Data were analyzed using the EPI Info Statistical Package version 6. A P-valuePremarital Screening Attitudes Hemoglobinopathies
The effectiveness and safety of thyroxine replacement therapy for children with down syndrome and subclinical or congenital hypothyroidism—A systematic review
Machinery throwing threshed grain into pile.GrayscaleSorensen Safety Negatives, Binder: North & Central America
Attitude toward Prenatal Testing and Termination of Pregnancy among Health Professionals and Medical Students in Saudi Arabia
AbstractThis study was aimed at assessing the attitude of health care professionals in Jeddah city toward prenatal diagnosis (PND) and termination of pregnancy (TOP). A cross-sectional study was conducted, and the participants completed a self-administered questionnaire. Approximately 82% of participants showed a consistent trend of accepting PND when appropriate, and 47.5% of the respondents were in favor of TOP if the fetus had a severe disease. Compared with men (69.3%), a significantly greater number of women (88%) accepted to have PND. The most acceptable prenatal diagnostic tests in the study were invasive techniques as most of the participants thought that noninvasive tests were nonspecific.</jats:p
Effect of Ramadan fasting in Saudi Arabia on serum bone profile and immunoglobulins
Background: Each year Muslims fast from dawn to sunset for 1 month (Ramadan). In Saudi Arabia, the sleep–wake cycle during Ramadan is severely disturbed and is associated with abolition of the circadian cortisol rhythm, exposing Saudis to continuously increased cortisol levels, which may influence the immune response. In addition to cortisol, sleep and fasting affect the secretion of parathyroid hormone (PTH) and hence bone metabolism. Methods: Our objective was to investigate the effect of Ramadan type fasting on secretory patterns of PTH, markers of bone metabolism, and serum immunoglobulins. Blood samples from healthy young volunteers were collected at 9 a.m. and 9 p.m. (± 1 hour) before (Shaban) and 2 weeks into Ramadan. Calcium, phosphorus, magnesium, albumin, alkaline phosphatase, 25-OH vitamin D, intact PTH (iPTH), and immunoglobulin (Ig) A, M and G were measured. Results: During Ramadan, evening-adjusted calcium was higher ( p = 0.036) and phosphate lower ( p < 0.001) than the corresponding morning value. Moreover, the Ramadan mean morning phosphate was higher and the evening level lower was than Shabaan values ( p = 0.010 and p <0.001, respectively), while mean iPTH level was decreased compared with the morning value ( p = 0.001), and the evening mean during Shabaan ( p = 0.029). Mean IgG concentration was significantly lower during Ramadan ( p = 0.003 and p = 0.021 for morning and evening, respectively). Conclusions: Changes in dietary practices during Ramadan modulated PTH secretion to a pattern which might be beneficial to bone health. Combined effects of fasting and disturbed sleep led to a noted decrease in IgG level. Therefore, a possible beneficial effect of fasting on bone turnover is combined with decreased immune response
Effect of Ramadan fasting in Saudi Arabia on serum bone profile and immunoglobulins
Background: Each year Muslims fast from dawn to sunset for 1 month
(Ramadan). In Saudi Arabia, the sleep-wake cycle during Ramadan is
severely disturbed and is associated with abolition of the circadian
cortisol rhythm, exposing Saudis to continuously increased cortisol
levels, which may influence the immune response. In addition to
cortisol, sleep and fasting affect the secretion of parathyroid hormone
(PTH) and hence bone metabolism.
Methods: Our objective was to investigate the effect of Ramadan type
fasting on secretory patterns of PTH, markers of bone metabolism, and
serum immunoglobulins. Blood samples from healthy young volunteers were
collected at 9 a.m. and 9 p.m. (+/- 1 hour) before (Shaban) and 2 weeks
into Ramadan. Calcium, phosphorus, magnesium, albumin, alkaline
phosphatase, 25-OH vitamin D, intact PTH (iPTH), and immunoglobulin (Ig)
A, M and G were measured.
Results: During Ramadan, evening-adjusted calcium was higher (p = 0.036)
and phosphate lower (p < 0.001) than the corresponding morning value.
Moreover, the Ramadan mean morning phosphate was higher and the evening
level lower was than Shabaan values (p = 0.010 and p < 0.001,
respectively), while mean iPTH level was decreased compared with the
morning value (p = 0.001), and the evening mean during Shabaan (p =
0.029). Mean IgG concentration was significantly lower during Ramadan (p
= 0.003 and p = 0.021 for morning and evening, respectively).
Conclusions: Changes in dietary practices during Ramadan modulated PTH
secretion to a pattern which might be beneficial to bone health.
Combined effects of fasting and disturbed sleep led to a noted decrease
in IgG level. Therefore, a possible beneficial effect of fasting on bone
turnover is combined with decreased immune response
Health Impact of Fasting in Saudi Arabia during Ramadan: Association with Disturbed Circadian Rhythm and Metabolic and Sleeping Patterns
Background: Muslims go through strict Ramadan fasting from dawn till
sunset for one month yearly. These practices are associated with
disturbed feeding and sleep patterns. We recently demonstrated that,
during Ramadan, circadian cortisol rhythm of Saudis is abolished,
exposing these subjects to continuously increased cortisol levels.
Hypothesis: Secretory patterns of other hormones and metabolic
parameters associated with cortisol, and insulin resistance, might be
affected during Ramadan.
Protocol: Ramadan practitioners (18 males, 5 females; mean age +/- SEM =
23.16 +/- 1.2 years) were evaluated before and two weeks into Ramadan.
Blood was collected for measurements of endocrine and metabolic
parameters at 9 am (+/- 1 hour) and again twelve hours later.
Results: In Ramadan, glucose concentration was kept within normal range,
with a significant increase in the morning. Mean morning concentration
of leptin was significantly higher than pre-Ramadan values (p = 0.001),
in contrast to that of adiponectin, which was significantly lower
(p<0.001). These changes were associated with increased insulin
resistance in morning and evening. Concentrations of hsCRP were lower
during Ramadan than those during regular living conditions, however,
normal circadian fluctuation was abolished (p = 0.49). Even though means
of liver enzymes, total bilirubin, total protein and albumin were all
decreased during Ramadan, statistically lower means were only noted for
GGT, total protein, and albumin (p = 0.018, 0.002 and 0.001
respectively).
Discussion: Saudi Ramadan practitioners have altered adipokine patterns,
typical of insulin resistance. The noted decreases of hsCRP, liver
enzymes, total protein, and albumin, are most likely a result of
fasting, while loss of circadian rhythmicity of hsCRP is probably due to
loss of circadian cortisol rhythm.
Conclusions: Modern Ramadan practices in Saudi Arabia, which are
associated with evening hypercortisolism, are also characterized by
altered adipokines patterns, and an abolished hsCRP circadian rhythm,
all likely to increase cardiometabolic risk